Angiotensin-converting Enzyme Concentration Research Articles

Serial investigation of Angiotensin-Converting Enzyme in sarcoidosis patients treated with Angiotensin-Converting Enzyme Inhibitor

Angiotensin-converting enzyme (ACE) is an acid glycoprotein that converts angiotensin I into angiotensin II. It is produced mainly by activated alveolar macrophages and it resulted elevated in sarcoidosis patients. ACE is the only biomarker mentioned in WASOG international guidelines for the diagnosis and follow-up of sarcoidosis patients but its sensitivity and specificity are low. This study aimed to analyze serial measurements of ACE levels in sarcoidosis patients stratified according to concomitant ACE-inhibitor therapies (ACEIs). 136 serum samples from sarcoidosis patients were retrospectively enrolled in the study. Serial ACE concentrations were measured once year for each patient. Population were divided according to radiogical stages and ACEIs. ACE concentrations resulted higher in non-ACEIs than ACEIs group (p<E-04). This result was confirmed also stratifying population according to radiological stages particularly in stage 3 (p=2E-03) or stage 2 of the disease (p<1E-04). Considering ACEIs, serum ACE levels proved to be higher in sarcoidosis patients treated with zofenopril than in those treated with perindopril (p=2E-02), enalapril (p=2E-03) or ramipril (p=2E-04). Patients treated with ACEIs showed a progressive reduction in ACE levels to five years of follow-up (p=1.3E-02) and the zofenopril group recorded the highest ACE levels (p<1E-04). This retrospective study investigated changes in ACE levels in patients with sarcoidosis treated or not treated with ACEIs. Considering the overall low sensitivity and specificity of this biomarker, we suggest systematically investigating medical drugs prescribed for patients with sarcoidosis, in order to optimize the interpretation of ACE in clinical management.

Inflammatory Bowel Diseases and COVID-19: The Invisible Enemy

Inflammatory Bowel Diseases and COVID-19: The Invisible Enemy

Genetic Association of ACE Polymorphism with Sarcopenia and Effects of Genetic Regulation of ACE Activity on Muscle Function

The purpose of this study was to investigate associations between skeletal muscle mass and ACE polymorphism, or sarcopenia‐related candidate gene, and to examine the effects of genetical angiotensin‐converting enzyme (ACE) activity on physical performance and respiratory muscle function in Korean adults. For this study, 1,464 Korean adults aged 18~79 were recruited. The anthropometrics were 1.69±0.06m (height), 63.1±5.5kg (weight), 29.4±6.5% (percent body fat), and 24.5±3.0kg/m2 (body mass index). Fat‐free mass, physical performance, gait speed (Timed Up‐and‐Go), pulmonary function (maximal inspiration and expiration pressure) and fatiguing maximum voluntary isometric contraction (40% MVIC) of ankle plantar flexor muscles with dynamic Electromyography were tested. Data of body composition and muscle functions were analyzed using one‐way ANOVA and post‐hoc Scheffe test for continuos variables and the Chi‐square test and host‐hoc Bonfferioni correction for countable variables. Blood samples for the whole blood and serum were obtained and assayed for circulating ACE activity and the ACE I/D genotype. The distribution of ACE polymorphism throughout the groups was analyzed using the Chi‐square test and host‐hoc Bonferroni correction for genetic distribution and multiple logistic regression analysis for the odds ratios (ORs) with 95% confidence intervals (CIs). We found that the distribution of ACE Indel genotype for sarcopenia was significantly different from normal population who have normal or high fat‐free mass index. Especially, we found a significantly higher (p&lt;.05) distribution of DD genotype in sarcopenia participants (27%) than the incidence (12.5%) in normal population. The D allele of ACE genotypes in older adults indicated significantly slower gait speed than I allele of them in the Timed Up‐and‐go test (p&lt;.05), and significantly lower levels for maximal inspiration and expiration pressure (p&lt;.05). The II genotype in older adults indicate the highest tolerance of muscle fatigue during muscle contraction (p&lt;.05). In conclusion, ACE Indel polymorphism and level of ACE activity is associated with sarcopenia in older adults and would genetically regulate muscle function in part. Our findings suggest that genetical concentrations of angiotensin‐converting enzyme should play a role in determining low muscle mass, slow walking speed, respiratory muscle function, and fatigue after muscle contraction in individuals. Therefore, examining ACE Indel polymorphism and ACE activity level could be used to predict sarcopenia and muscle function, and subsequently this information can be applicable to prevention and treatment to the aging muscle.Support or Funding InformationThis research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (358‐2011‐1‐G00025).

P417 Do ACE inhibitors and angiotensin II receptor blockers improve disease outcomes in inflammatory bowel disease?

Abstract Background The renin-angiotensin system (RAS) has an established role in the pathogenesis of fibrosis and inflammation in renal and cardiovascular disease. High concentrations of angiotensin-converting enzyme (ACE) and renin are found in the small and large bowel. This is elevated further within inflamed colonic tissue of inflammatory bowel disease (IBD) patients, compared with controls. (1) ACE inhibitor (ACEi) or angiotensin II receptor blocker (ARB) therapy may inhibit the effects of RAS in IBD. We aimed to examine the relationship between ACEi/ARB use and longitudinal disease activity outcomes in patients with IBD. Methods In a well-characterised cohort of IBD patients, followed up for a minimum of 2 years, baseline demographics and longitudinal disease activity were compared between patients using ACEi/ARB and those not. We reviewed case notes for flare or glucocorticosteroid use, escalation of medical therapy, hospitalisation, and intestinal resection. In univariate analyses, the χ² test was used to compare categorical variables and independent samples t-test for continuous data. A P value of &amp;lt;0.05 was considered statistically significant. Multivariate Cox regression analyses were expressed as hazard ratios (HR) with 95% confidence intervals (CI). Results In total, 764 patients with IBD (UC = 321, CD = 443) were included. There was no significant difference in baseline demographics (sex, ethnicity, and smoking) between those with ACEi/ARB use or non-use. Mean age was higher in those taking ACEi/ARBs (60 ± 13 vs. 41 ± 16). Univariate analyses showed a trend towards improved outcomes in those using ACEi/ARB, which was significant for intestinal resection (Table 1). Following multivariate Cox regression analysis, a continued trend of improved outcomes with ACEi/ARB use was observed (Graphs 2 and 3). Conclusion These data show a trend towards improved longitudinal disease activity outcomes in IBD patients using ACEi/ARBs. The study may be underpowered to detect a significant difference in these comparisons. Future studies performed in larger cohorts, with longer follow-up may yield significant results. Reference

ACE overexpression in myeloid cells increases oxidative metabolism and cellular ATP

ACE overexpression in myeloid cells increases oxidative metabolism and cellular ATP

Bioanalytical Assessment of Plasma Concentrations of Angiotensin-Converting Enzyme II Inhibitors and Angiotensin Receptor Blockers: A Pilot Study Among Patients Hospitalized With Acute Heart Failure.

Although angiotensin-converting enzyme II inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) improve chronic heart failure (HF) outcomes, their potential harms and benefits in acute HF (AHF) is less clear. We explored the relationship between ACEI or ARB plasma concentrations among patients with AHF with in-hospital change in estimated glomerular filtration rate (eGFR). From August 2016-June 2017, patients with AHF prescribed an outpatient ACEI or ARB were enrolled before AHF treatment. All patients were given twice their home dose of diuretic intravenously and received clinical care at the discretion of the medical team. Of 61 patients in the parent study, saved plasma from 34 who were prescribed an outpatient ACEI or ARB was included in this substudy. Liquid chromatography-tandem mass spectrometry was performed to assess ACEI or ARB plasma concentrations before AHF treatment. Change in eGFR was computed using the Chronic Kidney Disease Epidemiology Collaboration equation, which adjusts for age, sex, and race; diuretic dose and enrollment eGFR were used to adjust for HF severity. Multiple linear regression adjusting for enrollment eGFR and diuretic dose was performed to examine the relationship between drug concentration (undetectable/low vs. in/above-range) and in-hospital change in eGFR. Of 34 patients with AHF, median age was 63 years (interquartile range, 58-78 years), 19 (55.9%) were women, median eGFR at enrollment was 55.6 mL/min (interquartile range, 35.2-75.3 mL/min), and for 11 (32.4%), no ACEI or ARB was detectable in plasma. Medication concentrations in- or above-reference range were associated with in-hospital decrease in eGFR of 8.3 mL/min (95% confidence interval, 15.3-1.3 mL/min decrease), after adjusting for enrollment eGFR and diuretic treatment. Bioanalytical assessment of medication levels may be useful to guide in-hospital ACEI and ARB therapy for patients with AHF.

The effect of intravitreally administered angiogenesis inhibitor on the concentration of angiotensin-converting enzyme in the blood serum and lacrimal fluid in patients with diabetic macular edema

Diabetic retinopathy (DR) is one of the more serious complications of diabetes and the main cause of blindness among working-age individuals. In recent years, information has emerged on the possible role of the renin-angiotensin system (RAS) in the pathogenesis of DR, and DR's possible connection with the system of pro-angiogenic factors. To study the impact of anti-angiogenic therapy on systemic and local concentrations of angiotensin-converting enzyme (ACE), a key component of RAS, for patients with diabetic macular edema (DME). The concentration of ACE in the lacrimal fluid and blood serum in 10 patients (20 eyes) with DME was determined before and after intravitreal injection (IVI) of ranibizumab. The comparison group consisted of 7 patients (14 eyes) with age-related macular degeneration (AMD). The control group consisted of 10 healthy individuals (20 eyes). All groups were comparable in age and sex. The concentration of ACE was determined by enzyme immunoassay. The main group was examined four times: before IVI of ranibizumab, and then one week, two weeks and one month after IVI of ranibizumab. The comparison group was examined before, and then one week after, IVI of ranibizumab. In patients with DME, there was an initial 1.8-fold increase in the concentration of ACE in the lacrimal fluid of both eyes. A week after IVI of ranibizumab, the concentration of ACE in the lacrimal fluid began to decrease, reaching the control level after two weeks, and remaining there one month after IVI of ranibizumab. Initially, the concentration of ACE in the blood serum in patients with DME was 2.2 times lower than the control level. After IVI of ranibizumab there was an increase in the concentration of ACE in the blood serum, but by the end of the observation, the indicators continued to remain well below the control level. In patients with AMD, the initial concentration of ACE in the lacrimal fluids was not elevated; the concentration of ACE in the lacrimal fluids decreased 1.4 times one week after IVI of ranibizumab. The concentration of ACE in the blood serum of the patients with AMD was initially 25% lower than the control level, and essentially did not change after IVI of ranibizumab. СONCLUSIONS: Changes in the concentration of ACE in patients with DME may be a new prognostic criterion for the development of DME for patients with diabetes. These changes in the concentration of ACE, in the context of antiangiogenic therapy, indicate an interaction between the renin-angiotensin and angiogenic systems. Similar changes that were observed after IVI of ranibizumab in patients with AMD confirm the mutual influence of these two systems. The data presented in this study open up prospects for finding new pathways of pathogenic therapy for diabetic macular edema and diabetes.

Blood pressure lowering effect of Ficus deltoidea var kunstleri in spontaneously hypertensive rats: possible involvement of renin-angiotensin-aldosterone system, endothelial function and anti-oxidant system.

This study investigated the effects of a standardised ethanol and water extract of Ficus deltoidea var. Kunstleri (FDK) on blood pressure, renin-angiotensin-aldosterone system (RAAS), endothelial function and antioxidant system in spontaneously hypertensive rats (SHR). Seven groups of male SHR were administered orally in volumes of 0.5mL of either FDK at doses of 500, 800, 1000 and 1300mgkg- 1, or captopril at 50mgkg- 1 or losartan at 10mgkg- 1 body weight once daily for 4weeks or 0.5mL distilled water. Body weight, systolic blood pressures (SBP) and heart rate (HR) were measured every week. 24-hour urine samples were collected at weeks 0 and 4 for electrolyte analysis. At week 4, sera from rats in the control and 1000mgkg- 1 of FDK treated groups were analyzed for electrolytes and components of RAAS, endothelial function and anti-oxidant capacity. SBP at week 4 was significantly lower in all treatment groups, including captopril and losartan, when compared to that of the controls. Compared to the controls, ACE activity and concentrations of angiotensin I, angiotensin II and aldosterone were lower whereas concentrations of angiotensinogen and angiotensin converting enzyme 2 were higher in FDK treated rats. Concentration of eNOS and total anti-oxidant capacity were higher in FDK treated rats. Urine calcium excretion was higher in FDK treated rats. In conclusion, it appears that ethanol and water extract of FDK decreases blood pressure in SHR, which might involve mechanisms that include RAAS, anti-oxidant and endothelial system.

YKL-40, Soluble IL-2 Receptor, Angiotensin Converting Enzyme and C-Reactive Protein: Comparison of Markers of Sarcoidosis Activity

The aims of this study were to describe the clinical, radiological and immunological features of a population of sarcoidosis patients and to analyse chitinase-3-like protein 1 (YKL-40), soluble interleukin-2 receptor (sIL-2R), neopterin concentrations and adenosine deaminase (ADA) activity in serum of these patients in order to understand their potential as disease markers. Fifty-nine patients affected by chronic sarcoidosis, in active (20 patients) and inactive (39 patients) phase according to the clinical, radiological and laboratory criteria were studied. Serum YKL-40, sIL-2R, high-sensitive C-reactive protein (hs-CRP), neopterin levels and ADA activities were evaluated and compared with those of 25 healthy controls. Individuals with chronic sarcoidosis were significantly higher serum YKL-40, sIL-2R, neopterin, hs-CRP concentrations, angiotensin converting enzyme (ACE) and ADA activity than those of control subjects. Sarcoidosis patients in the active phase of the disease were significantly higher YKL-40, sIL-2R, hs-CRP levels and ACE activity than those in the inactive phase, while ADA activities and neopterin levels did not display any significant difference between the active and inactive disease groups. In comparison to the other parameters, as panel measurement of the serum YKL-40, sIL-2R, ACE and hs-CRP indicate a greater discrimination between active and inactive disease. The results indicate that serum YKL-40, sIL-2R, ACE and hs-CRP concentrations may be useful marker for monitoring sarcoidosis disease activity.

Biomarkers and Gene Polymorphisms in Members of Long- and Short-lived Families: A Longevity Study.

Background:The influence of biomarkers in human lifespan has been investigated but with no clear results yet.Materials and methods:Lipids, Uric Acid (UA), Adiponectin (ADIPOQ), Insulin-like Growth Factor (IGF-1), cholesteryl ester transfer protein (CETP) and angiotensin-converting enzyme (ACE) proteins, as well as CETP, ADIPOQ, insulin-like growth factor binding protein-3 (IGFBP3) and ACE-gene polymorphisms were evaluated in 149 Greek individuals. The Long-Lived Families (LON) (n=84) comprised of 3 generations: long-lived aged ≥90 years (P), offspring (FL1) and their grandchildren (FL2), while the Short-Lived Families (EAD) (n=65) where both parents died <75 years, comprised of 2 generations: middle-aged (FD1) and children (FD2).Results:Serum CETP and IGF-1 levels were lower, whereas AdipoQ concentrations were higher in P compared with FL1 and FL2 members (CETP: p = 0.03 for both comparisons; IGF-1 p < 0.001 for both comparisons and ADIPOQ: p = 0.001 and p = 0.004, respectively). Furthermore, serum triglycerides, UA and glucose concentrations were higher in FD1 compared with FD2 subjects (p=0.001, 0.02 and ≤0.001, respectively). In FD2 and FL2, CETP levels were lower in individuals with B2B2 compared with B1B1 genotype (p=0.007). Additionally, ACE concentrations were higher in individuals with DD compared with II genotype in both Families (p=0.001). After adjustment for age and gender, CETP levels were lower in P and FL2 individuals with B2B2 compared with the B1B1 genotype (p=0.004 and 0.007, respectively).Conclusion:Increase serum TGs, UA and GL concentrations were higher in the middle-aged individuals compared with their children in families independently of their lifespan. The serum adiponectin concentration was the highest in the oldest old individuals implying beneficial influence on lifespan. Independently of family’s lifespan history, the youngest individuals with CETPB2B2 genotype, compared with individuals with CETPB1B1 genotypes, had lower serum CETP concentrations. The knowledge of the unfavourable gene(s)influencing human lifespan may be helpful in encouraging individuals to follow healthier lifestyle habits and better control their high-risk biomarkers.

Blau Syndrome: An Unusual Cause of Hypercalcemia in a Child

Objective: To report a case of symptomatic vitamin D-mediated hypercalcemia in a girl with Blau syndrome, a rare granulomatous inflammatory disease occurring in early childhood. Methods: Clinical, laboratory, imaging, and genetic findings are presented along with response to therapy. Results: A 5-year-old girl with a history of surgically treated Graves disease presented with a serum calcium of 13.5 mg/dL (reference range is 9.6 to 10.6 mg/dL), phosphorus of 5.3 mg/dL (reference range is 3.7 to 5.4 mg/dL), parathyroid hormone of 6 pg/mL (reference range is 15 to 65 pg/mL), and an inappropriate 1,25-dihydroxyvitamin D3 of 64 pg/mL (reference range is 24 to 86 pg/mL). Her hypercalcemia was accompanied by painless, boggy joint effusions and hypertension. Additional testing revealed an elevated angiotensin-converting enzyme concentration and negative fungal and tuberculosis tests. Genetic testing revealed a mutation in the NOD2 gene, confirming the diagnosis of Blau syndrome. Hypercalcemia resolved with treat...

Angiotensin Converting Enzyme Inhibitor Has a Protective Effect on Decompression Sickness in Rats.

Introduction: Commercial divers, high altitude pilots, and astronauts are exposed to some inherent risk of decompression sickness (DCS), though the mechanisms that trigger are still unclear. It has been previously showed that diving may induce increased levels of serum angiotensin converting enzyme. The renin angiotensin aldosterone system (RAAS) is one of the most important regulators of blood pressure and fluid volume. The purpose of the present study was to control the influence of angiotensin II on the appearance of DCS.Methods: Sprague Dawley rats have been pre-treated with inhibitor of angiotensin II receptor type 1 (losartan; 10 mg/kg), angiotensin-converting enzyme (ACE) inhibitor (enalapril; 10 mg/kg), and calcium-entry blocker (nifedipine; 20 mg/kg). The experimental groups were treated for 4 weeks before exposure to hyperbaric pressure while controls were not treated. Seventy-five rats were subjected to a simulated dive at 1000 kPa absolute pressure for 45 min before starting decompression. Clinical assessment took place over a period of 60 min after surfacing. Blood samples were collected for measurements of TBARS, interleukin 6 (IL-6), angiotensin II (ANG II) and ACE.Results: The diving protocol induced 60% DCS in non-treated animals. This ratio was significantly decreased after treatment with enalapril, but not other vasoactive drugs. Enalapril did not change ANG II or ACE concentration, while losartant decreased post dive level of ACE but not ANG II. None of the treatment modified the effect of diving on TBARS and IL-6 values.Conclusion: Results suggests that the rennin angiotensin system is involved in a process of triggering DCS but this has to be further investigated. However, a vasorelaxation mediated process, which potentially could increase the load of inert gas during hyperbaric exposure, and antioxidant properties were excluded by our results.

Effect of an angiotensin-converting-enzyme inhibitor on the plasma concentration of cytokines and vasoactive molecules in patients with coronary heart disease and hypertension

To investigate the plasma concentrations of cytokines and vasoactive molecules in patients with coronary heart disease (CHD) in the presence of hypertension in relation to the angiotensin-converting-enzyme (ACE) inhibitor level reflecting the degree of renin-angiotensin-aldosterone system (RAAS) inhibition. 72 patients with NYHA functional class (FC) II-III angina pectoris and 40 healthy persons at the age of 47-65 years were examined in a controlled cohort study. Enzyme immunoassay was employed to determine the serum concentrations of interleukins (IL) (IL-2, IL-12, IL-17A, and IL-24), the vasoactive molecules of bradykinin, serotonin, ACE, angiotensin-II (AT-II), NO, and endothelin-1 (ET-1), and plasma renin activity. In addition, the plasma level of the tetrapeptide N-acetyl-Ser-Asp-Lys-Pro was used as a marker for ACE inhibition. The patients with CHD occurring in the presence of hypertension compared with the apparently healthy individuals displayed decreased ET-1 and NO production along with elevated levels of serotonin, AT-II, as well as IL-17A and IL-12. The found changes were accompanied by reduced renin activity. Thus, the individuals with low ACE inhibitor levels showed more pronounced production of the proinflammatory cytokine IL-17A, as well as high plasma concentrations of ACE and NO. The high ACE inhibitor level that reflects patient adherence to appropriate antihypertensive therapy is associated with the reduced production of IL-2 and with the minimum serum levels of ACE, AT-II, and NO, being characterized by the high production of IL-12 and serotonin at the same time. In patients with CHD and hypertension, the high plasma enzyme inhibitor concentration that reflects the activity of appropriate antihypertensive therapy, by contributing to the strengthening of the mechanisms of relaxation of blood vessels, is associated with the risk for proinflammatory activation of whole blood cells and platelets. The mean ACE inhibitor levels that reflect moderate RAAS suppression and are characterized by a relatively low proinflammatory activation of mononuclear cells may be more preferable than the maximum ones, from the point of view of slowing the progression of the subclinical inflammatory process of the vascular wall and preventing possible CHD exacerbations. This determines the feasibility of estimating the plasma level of an ACE inhibitor to control the depth of inhibition of RAAS activity.

Up-regulation of angiotensin-converting enzyme in response to acute ischemic stroke via ERK/NF-κB pathway in spontaneously hypertensive rats.

Cerebral ischemic stroke is usually caused by a temporary or permanent decrease in blood supply to the brain. Despite general progress in diagnosis and treatment, the prognosis of stroke is still unsatisfactory, and more detailed potential mechanisms are needed to investigate underlying the pathological process. Here, we showed that serum angiotensin-converting enzyme (ACE) concentration was positively correlated with infarct volume after acute ischemic stroke (AIS). Moreover, using a permanent middle cerebral artery occlusion rat model, we indicated for the first time that increased ACE expression in response to AIS was regulated by the ERK/NF-κB pathway in peri-infarct regions. More importantly, we disclosed that angiotensin II type 1 receptors were implicated in up-regulation of ACE expression in peri-infarct regions. These findings offer insight into ACE expression and activity in response to stroke, and further our understanding of ACE mechanisms.

ACE serum level and I/D gene polymorphism in children with obstructive uropathies and other congenital anomalies of the kidney and urinary tract

The aim of this study was to investigate the association of an insertion/deletion (I/D) polymorphism in angiotensin-converting enzyme (ACE) gene with serum ACE level in relation to the type and severity of malformations from congenital anomalies of the kidney and urinary tract (CAKUT) spectrum. A group of 134 Bulgarian children with CAKUT divided into four subgroups according to the leading malformation and 109 controls were genotyped by classical polymerase chain reaction. The quantitative determination of serum ACE was performed by ELISA method. A significant elevation of DD-genotype was observed in high-grade hydronephrosis compared to low-grade (43% vs. 9%). The carrying of DD-genotype was associated with higher risk for severe hydronephrosis with OR = 7.5 (95% CI: 1.242÷45.278; P = 0.028). Also, elevated serum ACE concentrations in patients with high-grade compared to low-grade hydronephrosis (237.4 ± 45 ng/mL vs 180.5 ± 64 ng/mL; P = 0.0065) were found. ACE level was significantly lower in patients with unilateral renal agenesis; hypo/dysplasia and multicystic dysplastic kidney (156.6 ± 54 ng/mL) than controls (200.6 ± 56.7 ng/mL; P = 0.005) and the remaining CAKUT subgroups. The DD genotype of I/D ACE polymorphism encodes the highest serum ACE level may be an additional genetic risk factor contributing to the severe hydronephrosis in Bulgarian patients with obstructive uropathies in contrast to other investigated categories of CAKUT malformations.

The angiotensin-converting enzyme insertion/deletion polymorphism rs4340 associates with habitual physical activity among European American adults.

BackgroundThe angiotensin‐converting enzyme (ACE) insertion/deletion (I/D) polymorphism (rs4340) (ACE DIP) accounts for half of the variability in plasma ACE concentrations. ACE has been widely studied for its influence on sports performance; however, research on its influence in physical activity is limited and inconsistent. We examined the influence of the ACE DIP on physical activity among 461 European Americans.MethodsSubjects completed the Paffenbarger Physical Activity Questionnaire for weekly walking distance. Multivariate analysis of covariance (MANCOVA) tested log‐transformed differences in weekly walking distance among ACE DIP genotypes (II, ID, DD) with gender as a fixed factor, and age and body mass index (BMI) as covariates. Because we found a significant ACE DIPxBMI interaction (P = 0.03), we categorized the sample by normal weight (NW: BMI<25.0 kg/m2) and overweight (OW: BMI ≥25.0 kg/m2) and repeated the MANCOVA with multiple comparison adjustments.Results NW adults with ACE II walked 15.8 ± 11.1 km/week, ID 13.2 ± 10.6 km/week, and DD 17.9 ± 13.0 km/week, with ID walking less than II (P = 0.03) and DD (P = 0.01). OW adults with ACE II walked 16.7 ± 12.6 km/week, ID 13.8 ± 11.6 km/week, and DD 9.7 ± 9.0 km/week, with DD walking less than II (P = 0.02). Weekly walking distance was 8.2 ± 2.4 km/week less among OW adults with ACE DD than NW (P = 0.02).Conclusion BMI interacted with ACE DD such that OW walked ~8.2 km/week less than NW, potentially equating to a body weight differential of ~3.5 kg annually.

Angiotensin-Converting Enzyme Gene Polymorphism in Children with Idiopathic Nephrotic Syndrome, Effect on Biopsy Findings

ABSTRACTObjective: Angiotensin converting enzyme (ACE) converts angiotensin I into angiotensin II. The ACE gene shows an I/D polymorphism, which correlates with ACE concentrations. The aim of this study is to evaluate the distribution of the ACE I/D genotype in children with idiopathic nephrotic syndrome (INS) and healthy controls and study the effect of this polymorphism on clinical and pathologic findings. Methods: ACE gene I/D polymorphism of 104 patients with INS and 119 controls were determined. Results: The DD, ID, and II genotypes were found in 58.7%, 22.1%, and 19.2% of the patients, and in 79.8%, 2.5%, and 17.6% of controls, respectively (p > 0.05). The ID genotype was seen more frequently in patients resistant to treatment. Conclusion: The observed differences with previous reports suggest the influence of the genetic background on disease course. The ACE I/D gene polymorphism's role seems to be more important in renal disease progression than susceptibility.

Urine RAS components in mice and people with type 1 diabetes and chronic kidney disease.

The pathways implicated in diabetic kidney disease (DKD) are largely derived from animal models. To examine if alterations in renin-angiotensin system (RAS) in humans are concordant with those in rodent models, we measured concentration of angiotensinogen (AOG), cathepsin D (CTSD), angiotensin-converting enzyme (ACE), and ACE2 and enzymatic activities of ACE, ACE2, and aminopeptidase-A in FVB mice 13-20 wk after treatment with streptozotocin (n = 9) or vehicle (n = 15) and people with long-standing type 1 diabetes, with (n = 37) or without (n = 81) DKD. In streptozotocin-treated mice, urine AOG and CTSD were 10.4- and 3.0-fold higher than in controls, respectively (P < 0.001). Enzymatic activities of ACE, ACE2, and APA were 6.2-, 3.2-, and 18.8-fold higher, respectively, in diabetic animals (P < 0.001). Angiotensin II was 2.4-fold higher in diabetic animals (P = 0.017). Compared with people without DKD, those with DKD had higher urine AOG (170 vs. 15 μg/g) and CTSD (147 vs. 31 μg/g). In people with DKD, urine ACE concentration was 1.8-fold higher (1.4 vs. 0.8 μg/g in those without DKD), while its enzymatic activity was 0.6-fold lower (1.0 vs. 1.6 × 109 RFU/g in those without DKD). Lower ACE activity, but not ACE protein concentration, was associated with ACE inhibitor (ACEI) treatment. After adjustment for clinical covariates, AOG, CTSD, ACE concentration, and ACE activity remained associated with DKD. In conclusion, in mice with streptozotocin-induced diabetes and in humans with DKD, urine concentrations and enzymatic activities of several RAS components are concordantly increased, consistent with enhanced RAS activity and greater angiotensin II formation. ACEI use was associated with a specific reduction in urine ACE activity, not ACE protein concentration, suggesting that it may be a marker of exposure to this widely-used therapy.

A role of endothelial dysfunction for development of microcirculation and cardiopulmonary blood flow abnormalities in patients with COPD and different alpha-1-antitrypsin phenotypes

The aim of this study was to investigate structural and functional changes of pulmonary vessels and cardiopulmonary blood flow in COPD patients with different alpha-1-antitrypsin (A1AT) phenotypes and endothelial dysfunction. Methods. Patients with COPD stage 2 to 3 (n = 113) with different A1AT phenotypes underwent clinical and radiological examination; endothelial dysfunction markers were measured. Results. More severe COPD was associated with more severe pulmonary microcirculation disorders and more significant perfusion defects. Patients with ZZ phenotype had worse pulmonary blood flow abnormalities compared to patients with MM phenotype. Pulmonary blood flow abnormalities were closely related to endothelial dysfunction (r = 0.75) and were more significant than structural abnormalities diagnosed on multi spiral computed tomography. Severe disorders of pulmonary blood flow were not accompanied by severe pulmonary hypertension. Conclusions: Blood levels of main endothelial dysfunction markers were directly related to COPD severity. Angiotensin-converting enzyme concentration was significantly below the normal level and was related to pulmonary artery pressure. The pulmonary blood flow differed in patients with different A1AT phenotypes and COPD stage 3 or higher. Perfusion defects were more severe in patients with ZZ phenotype.

Association of renin-angiotensin system genetic polymorphisms and aneurysmal subarachnoid hemorrhage.

OBJECTIVE Renin-angiotensin system (RAS) genetic polymorphisms are thought to play a role in cerebral aneurysm formation and rupture. The Cerebral Aneurysm Renin-Angiotensin System (CARAS) study prospectively evaluated common RAS polymorphisms and their relation to aneurysmal subarachnoid hemorrhage (aSAH). METHODS The CARAS study prospectively enrolled aSAH patients and controls at 2 academic centers in the United States. A blood sample was obtained from all patients for genetic evaluation and measurement of plasma angiotensin-converting enzyme (ACE) concentration. Common RAS polymorphisms were detected using 5' exonuclease (TaqMan) genotyping assays and restriction fragment length polymorphism analysis. RESULTS Two hundred forty-eight patients were screened, and 149 aSAH patients and 50 controls were available for analysis. There was a recessive effect of the C allele of the angiotensinogen ( AGT) C/T single-nucleotide polymorphism (SNP) (OR 1.94, 95% CI 0.912-4.12, p = 0.0853) and a dominant effect of the G allele of the angiotensin II receptor Type 2 ( AT2) G/A SNP (OR 2.11, 95% CI 0.972-4.57, p = 0.0590) on aSAH that did not reach statistical significance after adjustment for potential confounders. The ACE level was significantly lower in aSAH patients with the II genotype (17.6 ± 8.0 U/L) as compared with the ID (22.5 ± 12.1 U/L) and DD genotypes (26.6 ± 14.2 U/L) (p = 0.0195). CONCLUSIONS The AGT C/T and AT2 G/A polymorphisms were not significantly associated with aSAH after controlling for potential confounders. However, a strong trend was identified for a dominant effect of the G allele of the AT2 G/A SNP. Downregulation of the local RAS may contribute to the formation of cerebral aneurysms and subsequent presentation with aSAH. Further studies are required to elucidate the relevant pathophysiology and its potential implication in treatment of patients with aSAH.